Salmonella enterica is a major cause of disease in the United States and world-wide. This pathogen's increasing antibiotic resistance over the past decades has exacerbated its public health burden. To combat the rise in antibiotic resistance, it is necessary to understand how resistance spreads through the bacterial population. This requires study of the genes that determine resistance and also of the genetic relatedness of the isolates bearing those genes.

In this dissertation, three studies are presented. The aim of the first study was to examine the utility of multilocus sequence typing (MLST), which indexes sequence changes in housekeeping genes, for investigating genetic relatedness in S. enterica. MLST was shown to be a stable genetic typing method for S. enterica that is useful for long-term and global epidemiologic studies.

The aim of the second study was to examine the mechanisms of dissemination of antibiotic resistance genes mediated by a genetic structure called an integron, in a genetically diverse, global collection of S. enterica. Integrons are able to create variable collections of resistance genes and may be disseminated by horizontal gene transfer or by clonal expansion. Using MLST to determine genetic relatedness, the second study indicated that both of these mechanisms are important forces in the dissemination of integron mediated antibiotic resistance in S. enterica.

The investigation of integrons revealed three integrons not previously reported in S. enterica. The aim of the third study was to characterize those integrons, which contained novel aggregates of resistance genes, making them capable of conferring resistance to multiple antibiotics. One of these integrons was found in two genetically unrelated strains, reinforcing this structure's potential for contributing to horizontal gene transfer of antibiotic resistance in S. enterica.

Validation of MLST as a typing method for S. enterica has public health importance because it facilitates large scale and global studies of this organism by providing a basis for assessing genetic relatedness of diverse isolates. An understanding of the patterns of dissemination of integrons has public health significance because it enhances the ability to accomplish surveillance for changes in antibiotic resistance.